Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New research links body clocks to chronic lung diseases

18.03.2014

The body clock’s natural rhythm could be utilized to improve current therapies to delay the onset of chronic lung diseases.

Internal biological timers (circadian clocks) are found in almost all living things driving diverse processes such as sleep/wake cycles in humans to leaf movement in plants. In mammals including humans, circadian clocks are found in most cells and tissues of the body, and orchestrate daily rhythms in our physiology.

The research team’s ground breaking findings, which are being published in Genes & Development, have for the first time found that the circadian clock in the mouse lung rhythmically switches on and off genes controlling the antioxidant defense pathway. This 24 hourly rhythm enables the lungs to anticipate and withstand daily exposure to pollutants.

The research was led by Dr Qing-Jun Meng from The University of Manchester who is also a Medical Research Council (MRC) Research Fellow. He has been studying body clocks for a number of years and has been awarded an MRC Career Development Award to establish the relationship between the disruption of circadian rhythms and the susceptibility to human diseases, especially those associated with old age.

... more about:
»MRC »ageing »diseases »drugs »fibrosis »genes »pathway »pulmonary »rhythm

Dr Meng said: “We used a mouse model that mimics human pulmonary fibrosis, and found that an oxidative and fibrotic challenge delivered to the lungs during the night phase (when mice are active) causes more severe lung damages than the same challenge administered during the day which is a mouse’s resting phase.”

This means that the rhythm of this lung clock gives an indication of more suitable times of the day for drugs to be administered to patients suffering from oxidative/fibrotic diseases such as pulmonary fibrosis, asthma, chronic obstructive pulmonary disease.

Dr Meng continued: “Our findings show that timed administration of the antioxidant compound sulforaphane, effectively attenuates the severity of the lung fibrosis in this mouse model.”  
In other words the research suggests that taking drug treatments for oxidative and fibrotic diseases according to the lung clock time could increase their effectiveness, which would allow a lower dosage and consequently reduce side effects.

Dr Vanja Pekovic-Vaughan, who was part of the University’s research team, said: “This research is the first to show that a functioning clock in the lung is essential to maintain the protective tissue function against oxidative stress and fibrotic challenges. We envisage a scenario whereby chronic rhythm disruption (e.g., during ageing or shift work) may compromise the temporal coordination of the antioxidant pathway, contributing to human disease.” 

This latest study is part of on-going research that is exploring how chronic disruption to body clocks by changes like ageing or shift work contribute to a number of conditions such as osteoarthritis, cardiovascular disease, breast cancer, and mood disorder. 
Dr Meng said: “Our next step is to test our theory that similar rhythmic activity of the antioxidant defence pathway also operates in human lungs.  This will enable us to translate our findings and identify the proper clock time to treat chronic lung diseases that are known to involve oxidative stress.

“Funded by an MRC Fellowship Partnership Award, we have teamed up with GlaxoSmithKline to explore the potential of utilizing the body clock mechanisms to improve the efficiency of the current antioxidant compounds for diseases. Timing the delivery of drugs - so-called ’chrono-therapy’ or ’chrono-pharmacology’ - has already demonstrated clinical benefits in treatment of cancer and arthritis,” he said. 

Professor Stuart Farrow, a Director in the Respiratory therapy area at GSK (who is also the industrial partner for Dr Meng on the MRC Fellowship Partnership Award), commented: “Chronic lung diseases are prevalent and debilitating, and continue to be an important area of unmet medical need. This exciting new research reveals an opportunity to harness the body clock to provide valuable benefit to patients.” 

Notes for editors
Kath Paddison
Media Relations Officer
Faculty of Life Sciences
The University of Manchester
 
Tel. +44 (0)161 275 2111
Email: kath.paddison@manchester.ac.uk


Please contact us for a copy of the paper ‘The circadian clock regulates rhythmic activation of the NRF2/glutathionemediated antioxidant defense pathway to modulate pulmonary fibrosis’ by Vanja Pekovic-Vaughan, Julie Gibbs, Hikari Yoshitane, Nan Yang, Dharshika Pathiranage, Baoqiang Guo, Aya Sagami, Keiko Taguchi, David Bechtold, Andrew Loudon, Masayuki Yamamoto, Jefferson Chan, Gijsbertus T.J. van der Horst, Yoshitaka Fukada, Qing-Jun Meng

Kath Paddison | EurekAlert!
Further information:
http://www.manchester.ac.uk

Further reports about: MRC ageing diseases drugs fibrosis genes pathway pulmonary rhythm

More articles from Life Sciences:

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>